Project Summary
The physical inactivity (PIA) epidemic has far-reaching negative health impacts on adults, but
even more so on children, who are facing more PIA than ever in diverse forms. Although the
detrimental impacts of PIA on postnatal muscle are pronounced, and the negative impacts on
bone are well established across the lifecycle, the impact of early-life PIA on muscle and metabolic
health in adulthood is not fully realized. Thus, our objectives are 1) to investigate the effect of
the level of early-life physical inactivity in mice on the muscle quality and function phenotype in
adulthood, 2) to determine the root of muscle quality losses by examining the regulatory aspects
of the extracellular matrix (ECM) in adulthood, 3) to investigate the effect of the level of early-life
physical inactivity on frailty development and survival and 4) to expose undergraduate students
to meritorious biomedical research methods. We have piloted early-life PIA experiments, physical
performance tests, immunofluorescence methods, and data analysis with undergraduate
researchers and are prepared to complete this proposal. We have preliminary data indicating that
brief (2wk) early life PIA in mice produces weaker muscles, reduced muscle quality, increased
ECM, and decreased muscle macrophages 5 months later as adults. This equates to about half
a year of PIA during the first few years of life and early adulthood is about 25-30y of age for a
human. Our preliminary data suggest a concerning trajectory potentially characterized by
attenuated muscle quality and function -- all of which are associated with premature aging and
the possibility of rapid development of frailty and reduced lifespan. Thus, we aim to characterize
how the level of early life PIA, roughly equivalent to ~6 months human child, will contribute to
muscle quality (ECM changes) and physical function losses resulting from brief (2 weeks) early
life PIA during a key period of development in early adulthood (6 mo). The early life PIA will be
conducted with three levels of intensity with muscle disuse, reduced activity, and sedentary cage
activity compared to active control with running wheel access. We will examine skeletal muscle
ECM collagen content and structure, muscle macrophages, and ECM regulation in adult male
and female mice exposed to brief early-life PIA. Lastly, we will use physical performance testing
throughout aging to examine the effect of the development of frailty and survival curves in mice
exposed to brief early-life PIA
